The present study aimed to formulate orodispersible tablets of flutamide (FTM) to increase its bioavailability. Orodispersible tablets were prepared by direct compression technique using three different approaches namely; super-disintegration, effervescence and sublimation. Different combined approaches were proposed and evaluated to optimize tablet characteristics. Sodium starch glycolate (SSG) was used as the superdisintegrant. The prepared powder mixtures were subjected to both pre and post compression evaluation parameters including; IR spectroscopy, micromeritics properties, tablet hardness, friability, wetting time, disintegration time and in-vitro drug release. IR studies indicated that there was no interaction between the drug and the excipients used except Ludipress. The results of micromeritics studies revealed that all formulations were of acceptable to good flowability. Tablet hardness and friability indicated good mechanical strength. Wetting and dispersion times decreased from 46 to 38 s by increasing the SSG concentration from 3.33 to 6.66% w/w in tablets prepared by superdisintegration method. The F8 formulation which was prepared by combined approaches of effervescence and superdisintegrant addition gave promising results for tablet disintegration and wetting times but failed to give faster dissolution rate. The incorporation of 1:5 solid dispersion of FTM: PEG 6000 instead of the pure drug in the same formulation increased the drug release rate from 73.12 to 96.99% after 15 min. This increase in the dissolution rate may be due to the amorphization of the drug during the solid dispersion preparation. The presence of the amorphous form of the drug was shown in the IR spectra.
In an attempt to reach better treatment of skin infections, gel formulations containing Cefotaxime (CTX) were prepared. The gel was formulated using Carbopol 934 (C934), Hydroxypropyl Methylcellulose 4000 (HPMC 4000), Carboxymethylcellulose Sodium (Na CMC), Pectin (PEC), Xanthan Gum (XG), or Guar Gum (GG). Thirteen different formulas were prepared and characterized physically in terms of color, syneresis, spreadability, pH, drug content, and rheological properties. Drug-excipients compatibility studies were confirmed by FTIR and then in vitro drug release study was conducted. In vitro and in vivo antibacterial activities of CTX were studied against wound pathogens such as, Staphylococcus aureus (S. aureus), Escherichia coli (E. coli), and Pseudomonas aeruginosa (P. aeruginosa), using either pure drug or Fucidin® cream as control. F13 provides better spreadability compared to F1 (XG) or F11 (HPMC). Moreover, the release of the drug from hydrogel F13 containing C934 was slower and sustained for 8 h. Stability study revealed that, upon storage, there were no significant changes in pH, drug content, and viscosity of the gels. Also, F13 showed the larger inhibition zone and highest antibacterial activity among other formulations. Histological analysis demonstrated that after single treatment with F13 gel formulation, a noticeable reduction in microbial bioburden occurred in case of both Gram positive and Gram negative bacterial isolates.
The synthesis and molecular characterization of new isatin-based hydrazonoindolin-2-ones 4a-o and 7a-e are reported. The in vitro anti-proliferative potential of the synthesized compounds 4a-o and 7a-e was examined against HT-29 (colon), ZR-75 (breast) and A549 (lung) human cancer cell lines. Compounds 7b, 7d and 7e were the most active congeners against the tested human cancer cell lines with average IC50 values of 4.77, 3.39 and 2.37 μM, respectively, as compared with the reference isatin-based drug, sunitinib, which exhibited an average IC50 value of 8.11 μM. Compound 7e was selected for further pharmacological evaluation in order to gain insight into its possible mechanism of action. It increased caspase 3/7 activity by 2.4- and 1.85-fold between 4 and 8 h of treatment, respectively, at 10 μM and it caused a decrease in the percentage of cells in the G1 phase of the cell cycle with a corresponding increase in the S-phase. In addition, compound 7e increased phosphorylated tyrosine (p-Tyr) levels nearly two-fold with an apparent IC50 value of 3.8 μM. The 7e-loaded PLGA microspheres were prepared using a modified emulsion-solvent diffusion method. The average encapsulation efficiency of the 7e-loaded PLGA microspheres was 85% ± 1.3. While, the in vitro release profile of the 7e-loaded microspheres was characterized by slow and continuous release of compound 7e during 21 days and the release curve was fitted to zero order kinetics. Incorporation of 7e into PLGA microspheres improved its in vitro anti-proliferative activity toward the human cancer cell line A549 after 120 h incubation period with an IC50 value less than 0.8 μM.
Etodolac (ET) (poorly soluble drug) nanosuspensions were prepared by both pH shift method and antisolvent techniques in order to increase its dissolution rate. Various stabilizers were used, namely, Tween 20 and 80, HPMC, PVP K44, PVA, PEG 400, NaCMC, and -cyclodextrin. The prepared nanosuspensions were characterized by Fourier transform infrared spectroscopy (FTIR) and scanning electron microscope (SEM) and evaluated for their particle size, particle size distribution, and in vitro dissolution rate. In general, it was found that the antisolvent method for the preparation of ET nanosuspensions reduced the drug particle size to a higher extent compared to the pH shift method. The dissolution rate of ET in distilled water was markedly enhanced in the nanosized system, as more than 65% of drug dissolved in 10 min from all the nanosuspension formulations except F5 (stabilized with PVP K44) and F8 (stabilized with Tween 20), as compared to less than 20% of crude drug. Nanoparticles prepared by antisolvent method using Tween 80 as a stabilizer were selected for further in vivo study. The in vivo test demonstrated that nanoparticles of ET were well absorbed with a percentage drug absorption value 2.7 times more than that of micrometric size of crude ET.
Vancomycin HCl was prepared as orally administered colon target drug delivery tablets for systemic therapy. Tablet matrices containing 10–60% of tablet weight of guar gum (F1–F6) were prepared by direct compression and subjected to in vitro release studies to explore their sustained release in the colon. Various synthetic and natural polymers were incorporated to F6 to modify the drug release rate. Different 15 matrix tablet formulations (F6–F20) were enteric coated with hydroxypropyl methyl cellulose phthalate. F6, F13 and F20 showed promising sustained release results having median dissolution time (MDT) values: 8.25, 7.97, and 7.64, respectively. Microbiological assay was performed to test the efficacy of F6, F13, and F20 to inhibit clinical Staphylococcus aureus (SA) isolates. Bactericidal activity of F6 was reached after 2, 4, and 24 hours of incubation against MSSA 18, MRSA 29, and MRSA 11 strains, respectively, while it was reached within 6–8 hours in case of F13, and F20 against all strains tested. F13 enhanced log microbial reduction by 1.74, 0.65 and 2.4 CFU/mL compared to F6 while it was 1, 2.57 and 1.57 compared to F20 against MSSA18, MRSA11 and MRSA29, respectively. Vancomycin HCl tablets displayed a promising sustained release in vitro and microbiological inhibitory action on all isolates tested.
Drug repositioning is an important drug development strategy as it saves the time and efforts exerted in drug discovery. Since reepithelization of the cornea is a critical problem, we envisioned that the anticonvulsant phenytoin sodium can promote reepithelization of corneal ulcers as it was repurposed for skin wound healing. Herein, our aim is to develop novel crown ether-based nanovesicles “Crownsomes” of phenytoin sodium for ocular delivery with minimal drug-induced irritation and enhanced efficacy owing to “host–guest” properties of crown ethers. Crownsomes were successfully fabricated using span-60 and 18-crown-6 and their size, morphology, polydispersity index, ζ potential, drug loading efficiency, conductivity, and drug release were characterized. Crownsomes exhibited favorable properties such as formation of spherical nanovesicles of 280 ± 18 nm and −26.10 ± 1.21 mV surface charges. Crownsomes depicted a high entrapment efficiency (77 ± 5%) with enhanced and controlled-release pattern of phenytoin sodium. The optimum crownsomes formulation ameliorated ex vivo corneal drug permeability (1.78-fold than drug suspension) through the corneal calcium extraction ability of 18-crown-6. In vivo study was conducted utilizing an alkali-induced corneal injury rabbit model. Clinical and histopathological examination confirmed that crownsomes exhibited better biocompatibility and minimal irritation due to complex formation and drug shielding. Further, they enhanced corneal healing, indicating their effectiveness as a novel drug delivery system for ocular diseases.
A simple, sensitive, and accurate HPLC-DAD method has been developed and validated for the simultaneous determination of pantoprazole and etodolac in rat plasma as a tool for therapeutic drug monitoring. Optimal chromatographic separation of the analytes was achieved on a Waters Symmetry C18 column using a mobile phase that consisted of phosphate buffer pH~4.0 as eluent A and acetonitrile as eluent B in a ratio of A : B, 55 : 45 v/v for 6 min, pumped isocratically at a flow rate of 0.8 mL min−1. The eluted analytes were monitored using photodiode array detector set to quantify samples at 254 nm. The method was linear withr2=0.9999for PTZ andr2=0.9995for ETD at a concentration range of 0.1–15 and 5–50 μgmL−1for PTZ and ETD, respectively. The limits of detection were found to be 0.033 and 0.918 μgmL−1for PTZ and ETD, respectively. The method was statistically validated for linearity, accuracy, precision, and selectivity following the International Conference for Harmonization (ICH) guidelines. The reproducibility of the method was reliable with the intra- and interday precision (% RSD) <7.76% for PTZ and <7.58 % for ETD.
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